Research Project
Grant-in-Aid for Scientific Research (B)
The current study was aimed at visualizing all major hallmark pathologies of neurodegenerative dementias, consisting of fibrillary amyloid-beta, tau, alpha-synuclein, and TDP-43 protein aggregates, in the brains of living patients and animal models. Using original imaging agents for tau lesions, [11C]PBB3 and [18F]PM-PBB3, tau fibrils were found to accumulate in close association with clinical manifestations in Alzheimer’s disease, frontotemporal lobar degeneration, chronic traumatic encephalopathy, late-onset depression, and related disorders. The development of imaging probes for alpha-synuclein and TDP-43 pathologies made successful progress, yielding compounds that were immediately applicable to first-in-human PET studies. Notably, new imaging agents for alpha-synuclein deposits provided the first demonstration of in-vivo optical and PET imaging of disseminating alpha-synuclein fibrillization in rodent and non-human primate models.
アミロイドとタウ病変の生体脳イメージングにより、アルツハイマー病における両者の相互作用が示され、治療戦略上有用な情報が得られた。また、前頭側頭葉変性症や慢性外傷性脳症、高齢発症うつ病では、アミロイドよりもタウの沈着が発症や臨床症状に関連することが判明し、タウイメージングが診断や病勢評価に役立つ指標をもたらしうる。αシヌクレインおよびTDP-43病変プローブも臨床評価を開始できる段階まで開発が進み、世界に先駆けてヒトで病変の画像化が実現する可能性が高い。これにより、神経変性型認知症の100%近くを網羅する生体病理検査が可能になり、早期診断や治療介入ポイント決定に役立つ精密検査の実現が見込まれる。
All 2020 2019 2018 2017 2016 Other
All Int'l Joint Research (13 results) Journal Article (46 results) (of which Int'l Joint Research: 24 results, Peer Reviewed: 46 results, Open Access: 31 results, Acknowledgement Compliant: 2 results) Presentation (33 results) (of which Int'l Joint Research: 23 results, Invited: 32 results) Remarks (3 results) Patent(Industrial Property Rights) (3 results) (of which Overseas: 1 results)
Molecular Psychiatry
Volume: -
Nature Neuroscience
Nature Medicine
Volume: 26 Issue: 2 Pages: 281-288
10.1038/s41591-019-0723-9
J Neurosci.
Volume: 40 Issue: 17 Pages: 3491-3501
10.1523/jneurosci.2880-19.2020
Neurology and Clinical Neurocience
Volume: 8 Issue: 2 Pages: 61-7
10.1111/ncn3.12366
120007007732
J Alzheimers Dis.
Volume: 71 Issue: 1 Pages: 261-271
10.3233/jad-190620
Journal of Biological Chemistry
Volume: 294 Issue: 34 Pages: 12754-12765
10.1074/jbc.ra119.009487
Brain
Volume: 142 Issue: 10 Pages: 3265-3279
10.1093/brain/awz238
Journal of Medicinal Chemistry
Volume: 62 Issue: 5 Pages: 2362-2375
10.1021/acs.jmedchem.8b01576
The Open Biomedical Engineering Journal
Volume: 13 Issue: 1 Pages: 55-66
10.2174/1874120701913010055
Movement Disorders
Volume: 34 Issue: 5 Pages: 744-754
10.1002/mds.27643
Physics in Medicine & Biology
Volume: 64 Issue: 6 Pages: 065004-065004
10.1088/1361-6560/ab012c
Volume: 34 Issue: 4 Pages: 568-574
10.1002/mds.27623
Neurology
Volume: 92 Issue: 2
10.1212/wnl.0000000000006736
Current Alzheimer Research
Volume: 15 Issue: 11 Pages: 1062-1069
10.2174/1567205015666180709113338
Journal of Alzheimer's Disease
Volume: 64 Issue: s1 Pages: S353-S359
10.3233/jad-179933
European Journal of Nuclear Medicine and Molecular Imaging
Volume: 45 Issue: 9 Pages: 1605-1617
10.1007/s00259-018-4012-5
EJNMMI Research
Volume: 8 Issue: 1 Pages: 48-48
10.1186/s13550-018-0406-4
Journal of Neurology, Neurosurgery & Psychiatry
Volume: 89 Issue: 11 Pages: 1208-1214
10.1136/jnnp-2018-317970
International Journal of Molecular Sciences
Volume: 19 Issue: 5 Pages: 1497-1497
10.3390/ijms19051497
120006988072
Magnetic Resonance in Medical Sciences
Volume: 17 Issue: 4 Pages: 318-324
10.2463/mrms.mp.2017-0149
130007496873
Volume: 62 Issue: 4 Pages: 1539-1548
10.3233/jad-170749
EJNMMI research
Volume: 16 Issue: 1 Pages: 63-63
10.1186/s13550-017-0313-0
Volume: 61 Issue: 3 Pages: 1037-1052
10.3233/jad-170509
J. Nuclear Medicine
Volume: 117 Issue: 6 Pages: 960-966
10.2967/jnumed.117.201632
Frontiers in Neurology
Volume: 9 Pages: 70-70
10.3389/fneur.2018.00070
Glia
Volume: 66 Issue: 8 Pages: 1611-1624
10.1002/glia.23326
Frontiers in Neuroscience
Volume: 11 Pages: 723-723
10.3389/fnins.2017.00723
Movement Disorder
Volume: - Issue: 6 Pages: 884-892
10.1002/mds.27013
Volume: 8 Pages: 663-663
10.3389/fneur.2017.00663
Journal of Nuclear Medicine
Volume: - Issue: 10 Pages: 1652-1658
10.2967/jnumed.116.188698
International Journal of Neuropsychopharmacology
Volume: 20 Issue: 11 Pages: 928-935
10.1093/ijnp/pyx063
Nuclear Medicine and Biology
Volume: 55 Pages: 12-18
10.1016/j.nucmedbio.2017.08.002
PLoS One.
Volume: 12 Issue: 12 Pages: e0189318-e0189318
10.1371/journal.pone.0189318
Journal of Clinical Neuroscience
Volume: 46 Pages: 64-67
10.1016/j.jocn.2017.08.057
Volume: 20 Issue: 12 Pages: 957-962
10.1093/ijnp/pyx069
Volume: 32 Issue: 7 Pages: 1016-1024
10.1002/mds.27029
Biochemical Journal
Volume: 475 Issue: 1 Pages: 75-85
10.1042/bcj20170645
Alzheimer’s & Dementia (Amst)
Volume: 6 Issue: 1 Pages: 11-20
10.1016/j.dadm.2016.12.009
Acta Neuropathologica Communications
Volume: 5 Issue: 1 Pages: 12-14
10.1186/s40478-017-0413-0
Volume: 140 Pages: 764-780
10.1093/brain/aww339
Psychopharmacology
Volume: 234 Issue: 3 Pages: 323-328
10.1007/s00213-016-4464-x
J. Neuroscience
Volume: 36 Issue: 45 Pages: 11544-11558
10.1523/jneurosci.1279-16.2016
Scientific Reports
Volume: 6 Issue: 1 Pages: 34904-34904
10.1038/srep34904
120005850272
Journal of Neuroinflammation
Volume: 13 Issue: 1 Pages: 221-221
10.1186/s12974-016-0700-x
Theranostics
Volume: 6(8) Issue: 8 Pages: 1145-1159
10.7150/thno.15257
http://www.nirs.qst.go.jp/seika/brain/team/molecular_08.html
http://www.qst.go.jp/information/itemid047-003998.html
http://www.nirs.qst.go.jp/seika/brain/index.html